DESCRIPTION: The activity of many different types of molecules is modulated in the relevant neurons as an animal learns and stores information. Past research has focused on some of these types, such as molecules involved in second messenger metabolism, receptors, and some transcription factors. In Drosophila, the research has concentrated on molecules that are involved in cAMP-mediated signal transduction and that are expressed in mushroom body cells, neurons that appear to mediate olfactory learning in insects. These investigators are now turning their attention to molecules displayed at the surface of mushroom body cells, due to recent observations suggesting that a novel integrin and a surface member of the immunoglobulin superfamily of proteins are important for learning. A new learning mutant named volado, encodes an alpha-integrin expressed preferentially on mushroom body cells. In addition, products of the fasII gene, which encodes an NCAM-like molecule, are beautifully displayed on the axons of mushroom body cells and lesions of the gene produce deficits in olfactory classical conditioning. The proposed research will extend these observations to determine whether the deficits in conditioned behavior are general, or whether they are specific to olfactory classical conditioning. Conditional rescue experiments for both mutants are planned to help determine whether the lesions disrupt developmental processes that emerge as learning deficits, or whether the protein products are required physiologically during the process of learning. Candidates for the beta-integrin predicted to associate with the alpha-subunit will be evaluated for their roles in learning. Finally, genetic interaction studies are proposed to determine if these products are regulated by pathways of known importance; for example, the cAMP-mediated pathway, and whether there is an interaction between these two surface molecules. The investigators anticipate that the proposed research will reveal new insights and highlight the importance of cell surface molecules to the process of learning and memory. Furthermore, the identification of new molecules important for learning and memory will extend our knowledge, in general, of the molecular machinery underlying learning, and may provide insights into disease states that perturb cognitive processes.